Asthma exacerbations are associated with decreased quality of life and increased health care usage. Identification of characteristics that predict increased risk of future exacerbations in patients ...with suboptimal control of asthma could guide treatment decisions.
To examine patient characteristics associated with risk of asthma exacerbations in patients with uncontrolled persistent asthma.
A retrospective analysis of adults and children with inadequately controlled asthma despite asthma controller therapy and enrolled in 2 randomized trials was conducted. Baseline characteristics of subjects who experienced an asthma exacerbation during the treatment period were compared with those of subjects who did not experience an exacerbation.
Of 718 subjects (402 adults and 295 children), 108 adults (27%) and 110 children (37%) experienced an asthma exacerbation during the study period. Unscheduled health care visits for asthma or use of oral corticosteroids in the previous year were significantly associated with asthma exacerbation during the study period (P < .01). Adult subjects who experienced an exacerbation had significantly lower forced expiratory volume in 1 second compared with those who did not (2.3 vs 2.5 L, respectively, P = .02). Children who experienced an exacerbation had lower baseline pre- and post-bronchodilator ratios of forced expiratory volume in 1 second to forced vital capacity (77% vs 81%, P < .01; 82% vs 86%, P < .001, respectively). Symptom scores on validated questionnaires were significantly worse in adults but not in children who developed an exacerbation.
Spirometric measurements can help identify adults and children at increased risk for asthma exacerbation. Symptom scores could be helpful in identifying adults who are at high risk for exacerbations but could be less helpful in children.
Background Noninvasive sputum sampling has enabled the identification of biomarkers in asthmatic patients. Studies of discrete cell populations in sputum can enhance measurements compared with whole ...sputum in which changes in rare cells and cell-cell interactions can be masked. Objective We sought to enrich for sputum-derived human bronchial epithelial cells (sHBECs) and sputum-derived myeloid type 1 dendritic cells (sDCs) to describe transcriptional coexpression of targets associated with a type 2 immune response. Methods A case-control study was conducted with patients with mild asthma (asthmatic cases) and healthy control subjects. Induced sputum was obtained for simultaneous enrichment of sHBECs and sDCs by using flow cytometry. Quantitative PCR was used to measure mRNA for sHBEC thymic stromal lymphopoietin (TSLP) , IL33 , POSTN , and IL25 and downstream targets in sDCs (OX40 ligand OX40L , CCL17 , PPP1R14A , CD1E , CD1b , CD80 , and CD86 ). Results Final analyses for the study sample were based on 11 control subjects and 13 asthmatic cases. Expression of TSLP , IL33 , and POSTN mRNA was increased in sHBECs in asthmatic cases ( P = .001, P = .05, and P = .04, respectively). Expression of sDC OX40L and CCL17 mRNA was increased in asthmatic cases ( P = .003 and P = .0001, respectively). sHBEC TSLP mRNA expression was strongly associated with sDC OX40L mRNA expression ( R = 0.65, P = .001) and less strongly with sDC CCL17 mRNA expression. sHBEC IL33 mRNA expression was associated with sDC OX40L mRNA expression ( R = 0.42, P = .04) but not sDC CCL17 mRNA expression. Conclusions Noninvasive sampling and enrichment of select cell populations from sputum can further our understanding of cell-cell interactions in asthmatic patients with the potential to enhance endotyping of asthmatic patients.
Lessons From the World Trade Center Disaster Berger, Kenneth I., MD, FCCP; Reibman, Joan, MD; Oppenheimer, Beno W., MD ...
Chest,
07/2013, Volume:
144, Issue:
1
Journal Article
Peer reviewed
Open access
Background The present study (1) characterizes a physiologic phenotype of restrictive dysfunction due to airway injury and (2) compares this phenotype to the phenotype of interstitial lung disease ...(ILD). Methods This is a retrospective study of 54 persistently symptomatic subjects following World Trade Center (WTC) dust exposure. Inclusion criteria were reduced vital capacity (VC), FEV1 /VC > 77%, and normal chest roentgenogram. Measurements included spirometry, plethysmography, diffusing capacity of lung for carbon monoxide (D lco ), impulse oscillometry (IOS), inspiratory/expiratory CT scan, and lung compliance (n = 16). Results VC was reduced (46% to 83% predicted) because of the reduction of expiratory reserve volume (43% ± 26% predicted) with preservation of inspiratory capacity (IC) (85% ± 16% predicted). Total lung capacity (TLC) was reduced, confirming restriction (73% ± 8% predicted); however, elevated residual volume to TLC ratio (0.35 ± 0.08) suggested air trapping (AT). D lco was reduced (78% ± 15% predicted) with elevated D lco /alveolar volume (5.3 ± 0.8 mL/mm Hg/min/L). IOS demonstrated abnormalities in resistance and/or reactance in 50 of 54 subjects. CT scan demonstrated bronchial wall thickening and/or AT in 40 of 54 subjects; parenchymal disease was not evident in any subject. Specific compliance at functional residual capacity (FRC) (0.07 ± 0.02 L/cm H2 O/L) and recoil pressure (Pel) at TLC (27 ± 7 cm H2 O) were normal. In contrast to patients with ILD, lung expansion was not limited, since IC, Pel, and inspiratory muscle pressure were normal. Reduced TLC was attributable to reduced FRC, compatible with airway closure in the tidal range. Conclusions This study describes a distinct physiologic phenotype of restriction due to airway dysfunction. This pattern was observed following WTC dust exposure, has been reported in other clinical settings (eg, asthma), and should be incorporated into the definition of restrictive dysfunction.
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